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    Clinical Trial Results:
    Glucocorticoid Receptor Antagonism in the Treatment of Cushing Syndrome (GRACE): A Phase 3, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Study of the Efficacy and Safety of Relacorilant

    Summary
    EudraCT number
    		 2018-003096-35
    Trial protocol
    		 NL   BG   AT   PL   ES   DE   IT   RO  
    Global end of trial date
    15 Apr 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Jul 2025
    First version publication date
    10 Jul 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CORT125134-455
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03697109
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Corcept Therapeutics Incorporated
    Sponsor organisation address
    101 Redwood Shores Parkway, Redwood City, United States, 94065
    Public contact
    Medical Director, Corcept Therapeutics Incorporated, +1 650-327-3270, corceptstudy455@corcept.com
    Scientific contact
    Medical Director, Corcept Therapeutics Incorporated, +1 650-327-3270, corceptstudy455@corcept.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    15 Apr 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Apr 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This is a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study to assess the efficacy, safety and pharmacokinetics (PK) of relacorilant in patients with endogenous Cushing syndrome and concurrent type 2 diabetes mellitus/impaired glucose tolerance (DM/IGT) and/or uncontrolled hypertension (HTN). The first primary endpoint is the assessment of efficacy of relacorilant treatment based on sustained blood pressure control during the Randomized-withdrawal (RW) Phase, wherein patients who had achieved the blood pressure response criteria during the Open-label (OL) Phase are randomized to receive either relacorilant or placebo for 12 weeks. The second primary endpoint is assessment of safety as the number of patients with 1 or more treatment-emergent adverse events (TEAEs).
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Nov 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Poland: 5
    Country: Number of subjects enrolled
    Romania: 14
    Country: Number of subjects enrolled
    Spain: 12
    Country: Number of subjects enrolled
    Austria: 2
    Country: Number of subjects enrolled
    Bulgaria: 5
    Country: Number of subjects enrolled
    Germany: 6
    Country: Number of subjects enrolled
    Italy: 29
    Country: Number of subjects enrolled
    Israel: 4
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    United States: 70
    Worldwide total number of subjects
    152
    EEA total number of subjects
    76
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    127
    From 65 to 84 years
    25
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 404 patients were screened and 152 were enrolled.

    Period 1
    Period 1 title
    Open-label (OL) Phase
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Relacorilant (OL Phase)
    Arm description
    		 Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Relacorilant
    Investigational medicinal product code
    Other name
    CORT125134
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Relacorilant is supplied as 100 mg capsules for oral dosing.

    Number of subjects in period 1
    		Relacorilant (OL Phase)
    Started
    152
    Completed
    95
    Not completed
    57
         Adverse event, serious fatal
    2
         Consent withdrawn by subject
    21
         Physician decision
    2
         Adverse event, non-fatal
    24
         Lost to follow-up
    2
         Lack of efficacy
    6
    Period 2
    Period 2 title
    Randomized-withdrawal (RW) Phase
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Relacorilant (RW Phase)
    Arm description
    		 Patients who meet any of the response criteria will advance to the RW Phase of the study and receive the same dose of relacorilant as the last dose administered in the OL Phase.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Relacorilant
    Investigational medicinal product code
    Other name
    CORT125134
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Relacorilant is supplied as 100 mg capsules for oral dosing.

    Arm title
    		 Placebo (RW Phase)
    Arm description
    		 Patients who meet any of the response criteria will advance to the RW Phase of the study and receive placebo matched to study drug.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matched to study drug.

    Number of subjects in period 2 [1]
    		Relacorilant (RW Phase) Placebo (RW Phase)
    Started
    30
    32
    Completed
    27
    31
    Not completed
    3
    1
         Consent withdrawn by subject
    1
    1
         Adverse event, non-fatal
    1
    -
         Lack of efficacy
    1
    -
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Of the 95 patients who completed the OL Phase, 33 did not qualify or chose not to enter the RW Phase. Thus, a total of 62 patients entered the RW Phase of the study.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Relacorilant (OL Phase)
    Reporting group description
    		 Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily.

    Reporting group values
    		 Relacorilant (OL Phase) Total
    Number of subjects
    		 152 152
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 127 127
        From 65-84 years
    		 25 25
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 50.4 ( 13.23 ) -
    Gender categorical
    Units: Subjects
        Female
    		 127 127
        Male
    		 25 25
    Hypertension (HTN), Diabetes mellitus (DM), and impaired glucose tolerance (IGT) Status
    HTN is defined as mean systolic blood pressure (SBP) ≥135 or ≤170 mm Hg and/or mean diastolic blood pressure (DBP) ≥85 to ≤110 mm Hg. DM is defined as fasting plasma glucose ≥126 mg/dL and/or oral glucose tolerance test plasma glucose ≥200 mg/dL or hemoglobin A1c (HbA1c) ≥6.5%. IGT is defined as plasma glucose ≥140 mg/dL and <200 mg/dL on a 2-hour oral glucose tolerance test.
    Units: Subjects
        HTN only
    		 31 31
        DM or IGT only
    		 50 50
        HTN and DM/IGT
    		 71 71
    Body Weight
    Units: Kg
        arithmetic mean (standard deviation)
    		 93.77 ( 24.660 ) -
    Body Mass Index (BMI)
    Units: Kg/m^2
        arithmetic mean (standard deviation)
    		 34.738 ( 32.675 ) -
    Waist circumference
    Units: cm
        arithmetic mean (standard deviation)
    		 114.85 ( 18.0355 ) -

    End points

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    End points reporting groups
    Reporting group title
    Relacorilant (OL Phase)
    Reporting group description
    		 Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily.
    Reporting group title
    Relacorilant (RW Phase)
    Reporting group description
    		 Patients who meet any of the response criteria will advance to the RW Phase of the study and receive the same dose of relacorilant as the last dose administered in the OL Phase.

    Reporting group title
    Placebo (RW Phase)
    Reporting group description
    		 Patients who meet any of the response criteria will advance to the RW Phase of the study and receive placebo matched to study drug.

    Primary: Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase.

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    End point title
    		 Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase.
    End point description
    Loss of response with respect to HTN was measured using 6 criteria: 1) an increase in SBP of at least 5 mm Hg, 2) an increase in DBP of at least 5 mm Hg, 3) an increase in SBP and/or DBP of at least 5 mm Hg, 4) use of HTN rescue medication, 5) treatment discontinuation, and 6) missing 24-hour ambulatory blood pressure monitoring (ABPM) measurement at the end of the RW Phase. Blood pressure was measured using ABPM. Use of rescue medication was defined as any increase, modification, or addition of antihypertensive medication due to worsening HTN. Treatment discontinuation reports the number of patients who discontinued study treatment in the RW Phase for any reason. The analysis population was patients in the Intent-to-Treat (ITT-RW) Population who met the HTN response criteria at conclusion of the OL Phase. The ITT-RW Population included all patients who were randomized in the RW Phase and received at least 1 dose of study drug post randomization.
    End point type
    Primary
    End point timeframe
    Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
    End point values
    		 Relacorilant (RW Phase) Placebo (RW Phase)
    Number of subjects analysed
    21
    22
    Units: Patients
        SBP
    3
    1
        DBP
    1
    1
        SBP and/or DBP
    3
    4
        Use of rescue medication
    0
    7
        Treatment discontinuation
    2
    3
        Missing ABPM at end of RW Phase
    2
    3
    Statistical analysis title
    		 Difference in Loss of HTN Response
    Statistical analysis description
    The analysis is the difference in total count of patients losing HTN response between (continuing) relacorilant and placebo (withdrawing relacorilant) treatment in patients with initial HTN response to relacorilant.
    Comparison groups
    Relacorilant (RW Phase) v Placebo (RW Phase)
    Number of subjects included in analysis
    43
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence [1]
    P-value
    		 = 0.0215
    Method
    		 Chi-squared
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.04
         upper limit
    		 0.77
    Notes
    [1] - A logistic regression model with logit link function was used in order to detect if there was a significant difference in the proportion of patients with a loss of response with respect to hypertension under treatment with relacorilant compared with treatment with placebo in the RW Phase.

    Primary: Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0.

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    End point title
    		 Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0. [2]
    End point description
    The analysis population was patients in the Safety Population, which included all enrolled patients who received at least 1 dose of study drug.
    End point type
    Primary
    End point timeframe
    OL Phase: Up to 22 weeks; RW Phase: up to 18 weeks after completion of the OL Phase
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No between-group statistical analysis was planned or conducted for this endpoint.
    End point values
    		 Relacorilant (OL Phase) Relacorilant (RW Phase) Placebo (RW Phase)
    Number of subjects analysed
    152
    30
    32
    Units: Patients
    147
    23
    27
    No statistical analyses for this end point

    Secondary: Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) During the RW Phase

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    End point title
    		 Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) During the RW Phase
    End point description
    The analysis population was patients in the ITT-RW Population who had DM/IGT with or without HTN at Baseline.
    End point type
    Secondary
    End point timeframe
    Before and at time intervals up to 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
    End point values
    		 Relacorilant (RW Phase) Placebo (RW Phase)
    Number of subjects analysed
    18
    20
    Units: hours x mmol/L
        least squares mean (confidence interval 95%)
    1.91 (-1.138 to 4.966)
    4.81 (2.096 to 7.529)
    No statistical analyses for this end point

    Secondary: Change in Hemoglobin HbA1c During the RW Phase

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    End point title
    		 Change in Hemoglobin HbA1c During the RW Phase
    End point description
    The analysis population was patients in the ITT-RW Population who had DM/IGT with or without HTN at Baseline.
    End point type
    Secondary
    End point timeframe
    Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
    End point values
    		 Relacorilant (RW Phase) Placebo (RW Phase)
    Number of subjects analysed
    16
    19
    Units: Percentage of HbA1c
        least squares mean (confidence interval 95%)
    0.06 (-0.270 to 0.383)
    0.28 (-0.022 to 0.578)
    No statistical analyses for this end point

    Secondary: Change in 2-hour Plasma Glucose During the RW Phase

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    End point title
    		 Change in 2-hour Plasma Glucose During the RW Phase
    End point description
    Plasma glucose was measured using the 2-hour Oral Glucose Tolerance Test (oGTT). The analysis population was patients in the ITT-RW Population who had DM/IGT with or without HTN at Baseline.
    End point type
    Secondary
    End point timeframe
    Before and 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
    End point values
    		 Relacorilant (RW Phase) Placebo (RW Phase)
    Number of subjects analysed
    15
    19
    Units: mmol/L
        least squares mean (confidence interval 95%)
    0.52 (-1.06 to 2.09)
    2.96 (1.55 to 4.37)
    No statistical analyses for this end point

    Secondary: Change in SBP and DBP During the RW Phase

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    End point title
    		 Change in SBP and DBP During the RW Phase
    End point description
    Blood pressure was measured by 24-hour ABPM. The analysis population was patients in the ITT-RW Population who had HTN with or without DM/IGT at Baseline.
    End point type
    Secondary
    End point timeframe
    Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
    End point values
    		 Relacorilant (RW Phase) Placebo (RW Phase)
    Number of subjects analysed
    21
    22
    Units: mm Hg
    least squares mean (confidence interval 95%)
        SBP
    3.95 (0.470 to 7.424)
    10.43 (6.538 to 14.329)
        DBP
    2.86 (-0.199 to 5.928)
    6.53 (3.224 to 9.832)
    No statistical analyses for this end point

    Secondary: Change in Body Weight During the RW Phase

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    End point title
    		 Change in Body Weight During the RW Phase
    End point description
    The analysis population was patients in the ITT-RW Population.
    End point type
    Secondary
    End point timeframe
    Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
    End point values
    		 Relacorilant (RW Phase) Placebo (RW Phase)
    Number of subjects analysed
    26
    30
    Units: kg
        least squares mean (confidence interval 95%)
    -1.21 (-2.685 to 0.269)
    0.54 (-0.851 to 1.939)
    No statistical analyses for this end point

    Secondary: Number of Patients With Any Increase or Modification in Diabetes Medication During the RW Phase

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    End point title
    		 Number of Patients With Any Increase or Modification in Diabetes Medication During the RW Phase
    End point description
    The analysis population was patients in the ITT-RW Population who had DM/IGT at Baseline and received antidiabetic medication during the RW Phase.
    End point type
    Secondary
    End point timeframe
    Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase)
    End point values
    		 Relacorilant (RW Phase) Placebo (RW Phase)
    Number of subjects analysed
    7
    8
    Units: Patients
    1
    0
    No statistical analyses for this end point

    Secondary: Change in Cushing Quality of Life (QoL) Normalized Total Score During the RW Phase

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    End point title
    		 Change in Cushing Quality of Life (QoL) Normalized Total Score During the RW Phase
    End point description
    The Cushing QoL patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome, comprises 12 questions, each with 5 possible answers. The total score ranges from 12-60, with a higher score indicating improvement in QoL. The Cushing QoL instrument addresses known problem areas associated with Cushing syndrome including trouble sleeping, wound healing/bruising, irritability/mood swings/anger, self-confidence, physical changes, ability to participate in activities, interactions with friends and family, memory issues, and future health concerns. The analysis population was patients in the ITT-RW Population.
    End point type
    Secondary
    End point timeframe
    Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
    End point values
    		 Relacorilant (RW Phase) Placebo (RW Phase)
    Number of subjects analysed
    27
    31
    Units: Score on a scale
        least squares mean (confidence interval 95%)
    0.59 (-4.28 to 5.46)
    -0.58 (-5.14 to 3.98)
    No statistical analyses for this end point

    Other pre-specified: Percent Change in Tissue Fat Mass During the RW Phase

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    End point title
    		 Percent Change in Tissue Fat Mass During the RW Phase
    End point description
    Tissue fat mass was measured by dual energy X-ray absorptiometry (DXA) scan. Reported are change in in absolute tissue fat mass and change in percent tissue fat mass. The analysis population was patients in the ITT-RW Population.
    End point type
    Other pre-specified
    End point timeframe
    Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
    End point values
    		 Relacorilant (RW Phase) Placebo (RW Phase)
    Number of subjects analysed
    17
    22
    Units: Percent change
    least squares mean (confidence interval 95%)
        Absolute Tissue Fat Mass
    -0.64 (-1.684 to 0.400)
    1.67 (0.776 to 2.573)
        Percent Tissue Fat Mass
    -0.14 (-1.031 to 0.759)
    1.66 (0.887 to 2.437)
    No statistical analyses for this end point

    Other pre-specified: Number of Patients Who Worsened, as Assessed by the Global Clinical Response, During the RW Phase

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    End point title
    		 Number of Patients Who Worsened, as Assessed by the Global Clinical Response, During the RW Phase
    End point description
    The Global Clinical Response assessment measures the patient's signs and symptoms of endogenous hypercortisolism in 7 clinical categories: 1) glucose parameters, 2) blood pressure parameters, 3) body composition parameters, 4) clinical appearance, 5) strength parameters, 6) psychiatric health/cognitive function parameters, and 7) quality of life using the Cushing QoL score. The overall response based on the totality of signs and symptoms is rated as +1 for improved, 0 for unchanged, and -1 for worsened. Each patient's final score is the median of ratings given by 3 members of the Data Review Board.
    End point type
    Other pre-specified
    End point timeframe
    Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase)
    End point values
    		 Relacorilant (RW Phase) Placebo (RW Phase)
    Number of subjects analysed
    0 [3]
    0 [4]
    Units: Patients
    Notes
    [3] - End point data not reported
    [4] - End point data not reported
    No statistical analyses for this end point

    Other pre-specified: Change in Percent Tissue Fat Mass During the OL Phase

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    End point title
    		 Change in Percent Tissue Fat Mass During the OL Phase
    End point description
    Tissue fat mass was measured by DXA scan. The analysis population was patients in the modified ITT-OL (mITT-OL) Population including all enrolled patients who received at least 1 dose of study drug and had at least 1 postbaseline efficacy assessment.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Week 22 (end of OL Phase)
    End point values
    		 Relacorilant (OL Phase)
    Number of subjects analysed
    151 [5]
    Units: Percentage
    arithmetic mean (standard deviation)
        Baseline Percent Tissue Fat Mass OL Phase
    46.4 ( 8.39 )
        Change in Percent Tissue Fat Mass Week 22
    -1.8 ( 2.73 )
    Notes
    [5] - n=131 for Baseline value; n=71 for Change value
    No statistical analyses for this end point

    Other pre-specified: Change in Cushing QoL Normalized Total Score During the OL Phase

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    End point title
    		 Change in Cushing QoL Normalized Total Score During the OL Phase
    End point description
    The Cushing QoL patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome, comprises 12 questions, each with 5 possible answers. The total score ranges from 12-60, with a higher score indicating improvement in QoL. The Cushing QoL instrument addresses known problem areas associated with Cushing syndrome including trouble sleeping, wound healing/bruising, irritability/mood swings/anger, self-confidence, physical changes, ability to participate in activities, interactions with friends and family, memory issues, and future health concerns. The analysis population was patients in the mITT-OL Population.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Week 22 (end of OL Phase)
    End point values
    		 Relacorilant (OL Phase)
    Number of subjects analysed
    151 [6]
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Baseline Cushing QoL Score
    41.9 ( 19.78 )
        Change from Baseline in Cushing QoL Score
    7.4 ( 14.63 )
    Notes
    [6] - n=151 for Baseline value; n=99 for Change value
    No statistical analyses for this end point

    Other pre-specified: Change in Beck Depression Inventory-II (BDI-II) Score During the OL Phase

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    End point title
    		 Change in Beck Depression Inventory-II (BDI-II) Score During the OL Phase
    End point description
    The BDI-II is a 21-question self-report inventory that measures depression. Each answer is scored with values of 0 to 3. The total score ranges from 0 to 63. Scores of 0 to 13 indicate minimal depression, 14 to 19; mild depression; 20 to 28; moderate depression; 29 to 63; severe depression. The analysis population was patients in the mITT-OL Population.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Week 22 (end of OL Phase)
    End point values
    		 Relacorilant (OL Phase)
    Number of subjects analysed
    151 [7]
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Baseline BDI-II Score
    16.0 ( 10.24 )
        Change from Baseline in BDI-II Score at Week 22
    -2.8 ( 8.91 )
    Notes
    [7] - n=151 for Baseline value; n=99 for Change value
    No statistical analyses for this end point

    Other pre-specified: Mean Change From Baseline in Body Weight During the OL Phase

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    End point title
    		 Mean Change From Baseline in Body Weight During the OL Phase
    End point description
    The analysis population was patients in the mITT-OL Population.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Week 22 (end of OL Phase)
    End point values
    		 Relacorilant (OL Phase)
    Number of subjects analysed
    151 [8]
    Units: kg
    arithmetic mean (standard deviation)
        Baseline Body Weight
    93.82 ( 24.734 )
        Change from Baseline in Body Weight at Week 22
    -3.31 ( 5.861 )
    Notes
    [8] - n=151 for Baseline value; n=97 for Change value
    No statistical analyses for this end point

    Other pre-specified: Change in 2-hour Plasma Glucose During the OL Phase

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    End point title
    		 Change in 2-hour Plasma Glucose During the OL Phase
    End point description
    Plasma glucose was measured using the 2-hour oGTT. The analysis population was patients in the mITT-OL Population who had DM/IGT with or without HTN at Baseline.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Week 22 (end of OL Phase)
    End point values
    		 Relacorilant (OL Phase)
    Number of subjects analysed
    120 [9]
    Units: mmol/L
    arithmetic mean (standard deviation)
        Baseline oGTT
    14.370 ( 4.9402 )
        Change from Baseline in oGTT at Week 22
    -2.117 ( 4.6354 )
    Notes
    [9] - n=119 for Baseline value; n=71 for Change value
    No statistical analyses for this end point

    Other pre-specified: Change in Hemoglobin HbA1c During the OL Phase

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    End point title
    		 Change in Hemoglobin HbA1c During the OL Phase
    End point description
    The analysis population was patients in the mITT-OL Population who had DM/IGT at Baseline.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Week 22 (end of OL Phase)
    End point values
    		 Relacorilant (OL Phase)
    Number of subjects analysed
    120 [10]
    Units: Percentage of HbA1c
    arithmetic mean (standard deviation)
        Baseline HbA1c
    7.16 ( 1.626 )
        Change from Baseline in HbA1c at Week 22
    -0.29 ( 1.014 )
    Notes
    [10] - n=120 for Baseline value; n=74 for Change value
    No statistical analyses for this end point

    Other pre-specified: Change in SBP and DBP During the OL Phase

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    End point title
    		 Change in SBP and DBP During the OL Phase
    End point description
    Blood pressure was measured by 24-hour ABPM. The analysis population was patients in the mITT-OL Population who had HTN at Baseline.
    End point type
    Other pre-specified
    End point timeframe
    Baseline and Week 22 (end of OL Phase)
    End point values
    		 Relacorilant (OL Phase)
    Number of subjects analysed
    102 [11]
    Units: mm Hg
    arithmetic mean (standard deviation)
        Baseline SBP
    140.6 ( 10.66 )
        Change from Baseline in SBP at Week 22
    -7.9 ( 9.78 )
        Baseline DBP
    88.9 ( 7.20 )
        Change from Baseline in DBP at Week 22
    -5.4 ( 6.98 )
    Notes
    [11] - n=101 for the Baseline values; n=66 for the Change values
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    OL Phase: Up to 22 weeks; RW Phase: up to 18 weeks after completion of the OL Phase.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Relacorilant (OL Phase)
    Reporting group description
    		 Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily.

    Reporting group title
    Relacorilant (RW Phase)
    Reporting group description
    		 Patients who meet any of the response criteria will advance to the RW Phase of the study and receive the same dose of relacorilant as the last dose administered in the OL Phase.

    Reporting group title
    Placebo (RW Phase)
    Reporting group description
    		 Patients who meet any of the response criteria will advance to the RW Phase of the study and receive placebo matched to study drug.

    Serious adverse events
    		 Relacorilant (OL Phase) Relacorilant (RW Phase) Placebo (RW Phase)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    29 / 152 (19.08%)
    5 / 30 (16.67%)
    1 / 32 (3.13%)
         number of deaths (all causes)
    2
    0
    0
         number of deaths resulting from adverse events
    2
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant melanoma
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    3 / 152 (1.97%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Granuloma
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 30 (3.33%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    2 / 152 (1.32%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Mental status changes
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Acetabulum fracture
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Congenital mitral valve incompetence
         subjects affected / exposed
    0 / 152 (0.00%)
    0 / 30 (0.00%)
    1 / 32 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    2 / 152 (1.32%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Eye oedema
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diverticulum
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retroperitoneal haemorrhage
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 152 (1.32%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoporosis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bone abscess
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cavernous sinus thrombosis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 152 (0.66%)
    1 / 30 (3.33%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epididymitis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pseudomonal sepsis
         subjects affected / exposed
    1 / 152 (0.66%)
    1 / 30 (3.33%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinusitis fungal
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal osteomyelitis
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound abscess
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 30 (3.33%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    2 / 152 (1.32%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 152 (0.66%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 152 (0.66%)
    1 / 30 (3.33%)
    0 / 32 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Relacorilant (OL Phase) Relacorilant (RW Phase) Placebo (RW Phase)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    147 / 152 (96.71%)
    22 / 30 (73.33%)
    27 / 32 (84.38%)
    Investigations
    Blood pressure increased
         subjects affected / exposed
    0 / 152 (0.00%)
    0 / 30 (0.00%)
    2 / 32 (6.25%)
         occurrences all number
    0
    0
    2
    Vascular disorders
    Hypotension
         subjects affected / exposed
    10 / 152 (6.58%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    14
    0
    0
    Hypertension
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 30 (3.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    31 / 152 (20.39%)
    3 / 30 (10.00%)
    4 / 32 (12.50%)
         occurrences all number
    57
    3
    8
    Dizziness
         subjects affected / exposed
    23 / 152 (15.13%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    28
    0
    0
    Paraesthesia
         subjects affected / exposed
    21 / 152 (13.82%)
    2 / 30 (6.67%)
    0 / 32 (0.00%)
         occurrences all number
    30
    5
    0
    Neuropathy peripheral
         subjects affected / exposed
    13 / 152 (8.55%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    14
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 30 (3.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    2
    2
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    50 / 152 (32.89%)
    2 / 30 (6.67%)
    1 / 32 (3.13%)
         occurrences all number
    60
    3
    1
    Fatigue
         subjects affected / exposed
    34 / 152 (22.37%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    41
    0
    0
    Asthenia
         subjects affected / exposed
    19 / 152 (12.50%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    19
    0
    0
    Peripheral swelling
         subjects affected / exposed
    15 / 152 (9.87%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    19
    0
    0
    Pain
         subjects affected / exposed
    13 / 152 (8.55%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    13
    0
    0
    Pyrexia
         subjects affected / exposed
    0 / 152 (0.00%)
    2 / 30 (6.67%)
    0 / 32 (0.00%)
         occurrences all number
    0
    2
    0
    Blood and lymphatic system disorders
    Increased tendency to bruise
         subjects affected / exposed
    0 / 152 (0.00%)
    2 / 30 (6.67%)
    0 / 32 (0.00%)
         occurrences all number
    0
    2
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    52 / 152 (34.21%)
    2 / 30 (6.67%)
    1 / 32 (3.13%)
         occurrences all number
    78
    2
    1
    Diarrhoea
         subjects affected / exposed
    28 / 152 (18.42%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    32
    0
    0
    Abdominal pain upper
         subjects affected / exposed
    23 / 152 (15.13%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    31
    0
    0
    Constipation
         subjects affected / exposed
    23 / 152 (15.13%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    24
    0
    0
    Vomiting
         subjects affected / exposed
    19 / 152 (12.50%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    24
    0
    0
    Abdominal pain
         subjects affected / exposed
    17 / 152 (11.18%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    19
    0
    0
    Dyspepsia
         subjects affected / exposed
    8 / 152 (5.26%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    8
    0
    0
    Skin and subcutaneous tissue disorders
    Skin hyperpigmentation
         subjects affected / exposed
    24 / 152 (15.79%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    31
    0
    0
    Acne
         subjects affected / exposed
    12 / 152 (7.89%)
    3 / 30 (10.00%)
    0 / 32 (0.00%)
         occurrences all number
    12
    3
    0
    Dry skin
         subjects affected / exposed
    9 / 152 (5.92%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    9
    0
    0
    Rash
         subjects affected / exposed
    9 / 152 (5.92%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    13
    0
    0
    Pruritus
         subjects affected / exposed
    8 / 152 (5.26%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    9
    0
    0
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    12 / 152 (7.89%)
    0 / 30 (0.00%)
    4 / 32 (12.50%)
         occurrences all number
    14
    0
    4
    Irritability
         subjects affected / exposed
    0 / 152 (0.00%)
    2 / 30 (6.67%)
    0 / 32 (0.00%)
         occurrences all number
    0
    2
    0
    Depression
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 30 (3.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    2
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    43 / 152 (28.29%)
    2 / 30 (6.67%)
    2 / 32 (6.25%)
         occurrences all number
    83
    2
    2
    Back pain
         subjects affected / exposed
    41 / 152 (26.97%)
    5 / 30 (16.67%)
    6 / 32 (18.75%)
         occurrences all number
    59
    6
    8
    Arthralgia
         subjects affected / exposed
    30 / 152 (19.74%)
    3 / 30 (10.00%)
    3 / 32 (9.38%)
         occurrences all number
    56
    4
    6
    Myalgia
         subjects affected / exposed
    21 / 152 (13.82%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    29
    0
    0
    Muscular weakness
         subjects affected / exposed
    17 / 152 (11.18%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    20
    0
    0
    Muscle spasms
         subjects affected / exposed
    9 / 152 (5.92%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    11
    0
    0
    Bursitis
         subjects affected / exposed
    0 / 152 (0.00%)
    3 / 30 (10.00%)
    0 / 32 (0.00%)
         occurrences all number
    0
    3
    0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    11 / 152 (7.24%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    11
    0
    0
    Covid-19
         subjects affected / exposed
    9 / 152 (5.92%)
    2 / 30 (6.67%)
    0 / 32 (0.00%)
         occurrences all number
    9
    2
    0
    Folliculitis
         subjects affected / exposed
    0 / 152 (0.00%)
    1 / 30 (3.33%)
    2 / 32 (6.25%)
         occurrences all number
    0
    1
    4
    Nasopharyngitis
         subjects affected / exposed
    0 / 152 (0.00%)
    0 / 30 (0.00%)
    3 / 32 (9.38%)
         occurrences all number
    0
    0
    3
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    17 / 152 (11.18%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    17
    0
    0
    Hypokalaemia
         subjects affected / exposed
    8 / 152 (5.26%)
    0 / 30 (0.00%)
    0 / 32 (0.00%)
         occurrences all number
    9
    0
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Jun 2019
    Clarified the definition of study endpoints and statistical methods on estimation of safety, tolerability, and preliminary efficacy.
    29 Oct 2019
    1. Outlined methods to determine when rescue therapy (not resulting in unblinding of study treatment) should be initiated. 2. Added use of an unblinded Medical Monitor. 3. Specified which study-assessment results should remain blinded.
    20 Dec 2019
    1. Implementation of changes noted in Clarification Memo dated 06 December 2019 which includes: Clarification that only surgeries associated with radiation therapy are excluded during the study, and clarification of the allowable window for the administration of study drug in relation to the completion of the 2-hour oGTT test. 2. Revised text for rescue criterion in the RW Phase.
    17 Dec 2020
    1. Added section to address potential protocol modifications arising from the COVID-19 pandemic that accounts for all deviations and ensures appropriate safety monitoring is followed for trial participants. 2. Modified exclusion criteria based on regulatory agency input. 3. Clarified that dose increases of relacorilant will occur as tolerated and based on improvement in signs and symptoms of Cushing syndrome. 4. Added factors used for the determination of clinical benefit required for patients to continue relacorilant treatment in an extension study. 5. Clarified that if all symptoms of Cushing syndrome have resolved, no dose escalation will occur. 6. Clarified the conditions under which faster dose escalation for patients whose Cushing syndrome deteriorates may be allowed. 7. Added rescue criterion for initiating or increasing rescue medication for patients in the DM/IGT only subgroup. 8. Added details on assessments to be performed in the event rescue medication is used before Visit RW12. 9. Revised criteria for when patients should discontinue study drug/study participation and revised and clarified when return visits should occur following ET. 10. Added secondary efficacy endpoints and revised others for clarity. 11. Added exploratory efficacy endpoints. 12. Altered assessments at certain visits, so that 2-hour oGTT and HbA1c will be performed for all patients (not only DM/IGT patients) and ABPM (24-hour) will be performed for all patients (not only hypertension patients). 13. Decreased the maximum time between Visit OL22 and randomization to the RW Phase from 4 weeks to 2 weeks. 14. Changed procedure for ABPM (24-hour) prior to the RW12 study visit so it’s completed by the patient at home within 7 days of RW12 visit, rather than initiated in the clinic.
    05 Apr 2023
    1. Primary and secondary objectives were revised. 2. Primary, secondary, and exploratory endpoints were revised. 3. The number of patients planned to be enrolled in the study and statistical analyses were revised. 4. Conditions for entry to the RW Phase were revised. 5. The factors for assessing clinical benefit were revised. 6. An inclusion criterion was revised, and an exclusion criterion was revised, and one was added. 7. The dose-escalation process was revised. 8. Conditions regarding screening assessments were revised. 9. The conditions regarding Cushing syndrome medication washout were revised. 10. UFC sample collection requirements were revised. 11. Conditions regarding the salivary cortisol test were revised. 12. Procedure for monitoring AEs was revised and text regarding AE expectedness criteria was revised/deleted. Documentation and follow-up of AEs was also revised. Procedure for informing about pregnancy was revised. 13. Text was added regarding prioritizing safety assessments in the event of COVID-19 restrictions. 14. A section regarding data protection was added. 15. Administrative considerations were revised to be consistent among study protocols.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Two protocol amendments occurred after patient enrollment was completed and included revisions to study endpoints and their analysis methods. These amendments are not included in the Substantial Protocol Amendments (Globally) list.
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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